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人源环状RNA Hsa_circ_0003356通过miR-556-5p/FKBP5轴抑制胃癌进展。

Hsa_circ_0003356 suppresses gastric cancer progression via miR-556-5p/FKBP5 axis.

作者信息

Lu Chuanhui, Wu Jing, Li Xiaoguang, Huang Wei, Fang Yongmu, Huang Ying

机构信息

Department of Colorectal Cancer Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine. The School of Clinical Medicine,Fujian Medical University, Fuzhou, Fujian 350122, China.

Department of the Oncology, The Fifth Hospital of Wuhan, Wuhan, HuBei 430050, China.

出版信息

Toxicol In Vitro. 2024 May;97:105787. doi: 10.1016/j.tiv.2024.105787. Epub 2024 Feb 22.

Abstract

BACKGROUND

CircRNAs are implicated in the tumorigenesis of various human cancers. This study aims to explore how circ_0003356 contributes to the development of gastric cancer (GC).

METHODS

Circ_0003356 expression was analyzed in GSE184882 dataset and validated in our cohort of GC patients and human GC cell lines. The correlations between circ_0003356 levels and prognostic parameters were analyzed. The contribution of circ_0003356 in GC cell malignant behaviors such as cell survival, apoptosis and invasion were investigated by circ_0003356 overexpression in GC cell lines. The downstream targets of circ_0003356 were predicted and verified in vitro and in vivo. The in vivo function of circ_0003356 was studied as well in a xenograft mouse model.

RESULTS

Circ_0003356 expressed at a low level in human GC tissues and cells, which was closely associated with poor outcome of GC patients. Circ_0003356 overexpression induced GC cell apoptosis while depressed the growing, migration and invasive abilities through miR-556-5p/FKBP5 axis. In vivo model showed retarded tumor growth when circ_0003356-overexpressed cells were inoculated.

CONCLUSION

Circ_0003356 is identified as a potential biomarker of the prognosis of human gastric cancer, and circ_0003356/miR-556-5p/FKBP5 axis could be a promising target in gastric cancer treatment.

摘要

背景

环状RNA(circRNAs)与多种人类癌症的肿瘤发生有关。本研究旨在探讨circ_0003356如何促进胃癌(GC)的发展。

方法

在GSE184882数据集中分析circ_0003356的表达,并在我们的GC患者队列和人GC细胞系中进行验证。分析circ_0003356水平与预后参数之间的相关性。通过在GC细胞系中过表达circ_0003356,研究其在GC细胞恶性行为如细胞存活、凋亡和侵袭中的作用。在体外和体内预测并验证circ_0003356的下游靶点。还在异种移植小鼠模型中研究了circ_0003356的体内功能。

结果

circ_0003356在人GC组织和细胞中低表达,这与GC患者的不良预后密切相关。circ_0003356过表达诱导GC细胞凋亡,同时通过miR-556-5p/FKBP5轴抑制其生长、迁移和侵袭能力。体内模型显示,接种过表达circ_0003356的细胞后肿瘤生长受到抑制。

结论

circ_0003356被确定为人类胃癌预后的潜在生物标志物,circ_0003356/miR-556-5p/FKBP5轴可能是胃癌治疗的一个有前景的靶点。

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